University of Vermont

University Communications

Sholler Studies Old Drug for Neuroblastoma Treatment

Release Date: 06-29-2010

Author: Jennifer Ingersoll

A new pediatric clinical trial sponsored by the Vermont Cancer Center at the University of Vermont (UVM) and Vermont Children's Hospital at Fletcher Allen and led by physician-scientist Giselle Sholler, M.D., has opened to test the investigational drug DFMO, or alpha-difluoromethylornithine, as a treatment for neuroblastoma. The Phase I study is monitoring the safety of DFMO alone and in combination with a second drug, etoposide, among neuroblastoma patients and is determining whether the drug is effective in reducing or eradicating neuroblastoma tumor cells.

Each year, approximately 650 children in the U.S. are diagnosed with neuroblastoma, a rare cancer that occurs when malignant cells form in the sympathetic nervous system, often causing tumors in the adrenal gland, neck, chest, or abdomen. The disease is usually diagnosed in children less than six years of age. While many infants less than a year old may experience complete regression of primary tumors, older children are often confronted with metastatic neuroblastoma that is aggressive and responds poorly to even the most intense multi-component chemotherapy treatments.

DFMO, an FDA-approved drug therapy for African sleeping sickness, has demonstrated few side effects for patients. In recent years, the drug has attracted renewed interest from researchers as a treatment with great potential for certain cancers. DFMO is an inhibitor that specifically targets a key protein called ornithine decarboxylase (ODC). This protein makes polyamine molecules, which along with ODC, contribute to tumor development.

"DFMO is a very promising drug," said Sholler. "It's exciting to have this oral option available for children with relapsed neuroblastoma who have had aggressive previous therapy and are unable to tolerate further chemotherapies."

Sholler has also developed several FDA-approved clinical trials for treating relapsed neuroblastoma, which were opened nationally through the UVM-led Neuroblastoma and Medulloblastoma Translational Research Consortium. These trials are attracting national attention from pediatric cancer research specialists and from dozens of families from around the world.

As part of the DFMO study, Sholler is collaborating with colleague André Bachmann, Ph.D., M.S., associate professor at the University of Hawaii's Cancer Research Center, who has tested DFMO's effect on neuroblastoma cells in vitro. Bachmann's results were encouraging, prompting him and Sholler to team up to successfully demonstrate evidence of the drug's ability to cure neuroblastoma cancers in mice by inhibiting ODC, which is implicated in aggressive tumor development. The two scientists are continuing their research collaboration in moving these laboratory findings to an actual drug trial with analysis of bone marrow metastases from trial patients being conducted in Bachmann's research laboratory at the Cancer Research Center in Hawaii.

"Based on adult cancer studies, we expect this drug to be well tolerated with minimal side effects," says Sholler. "We are also hopeful that this trial will show response as well as improve quality of life for children living with this disease, allowing them to spend less time at the hospital and more time with their families."

The trial is expected to open at additional sites within the Neuroblastoma and Medulloblastoma Translational Research Consortium, including Kapiolani Medical Center in Honolulu. For more information, visit DFMO Study.